All Things Small and Great

Exposing the Unseen

Why did it take so long to acknowledge our inner microbe? The answer stems, in part, from the fact that most bacteria cannot be grown in the laboratory. Consequently, until recently, microbiologists could not identify—let alone understand—microbes that refused to live in the world of Petri dishes and culture flasks. Until recently, if we had been interested in describing microbial diversity, we would have collected a sample from some well-defined habitat—a hot spring or a water-treatment plant, for instance—then spread that sample on a variety of culture media and waited to see what grew. Yet for a long time, microbiology has known that only a tiny, biased sliver of microbial diversity could be cultured in the lab. As a result, we could guess, but we could never really know, what was out there.

Today the procedure is different. Over the past decade the constraints of the laboratory have been lifted. New methods in molecular biology now make it possible to identify microorganisms without having to grow them in the lab. These new methods rely on our ability to read the DNA sequence from certain deeply informative stretches of the genome, stretches that are unique to every microorganism. We now collect samples and identify the resident microbial species without having to grow them in the lab. Instead, we disrupt their outer membranes and so release their DNA. The resulting mix of DNA contains the genomes of every microbe in the sample. We then amplify short, distinctive, species-specific fragments from this DNA mixture, revealing the identity of virtually every microbe in that sample. Imagine the heavens first seen through a telescope—such is the impact of these new approaches on our conception of the diversity and complexity of microbial communities. We no longer glimpse stars; now we can comprehend galaxies.

Equipped with these new molecular tools, we have refocused our attention on the microorganisms living on and in us. From the outset, these studies suggest that human microbiota are more diverse, more complex, more structured and more fascinating than we could have imagined. Hundreds, possibly thousands, of different species make us their home. But is this diversity just the result of living in a world dense with microbes? Do our surface cracks and crevices simply collect microbial dust? Far from it. Each location in the human body appears to harbor its own structured, organized and site-specific community. These communities reflect the characteristics of the specific environments: the crook of your elbow is not, in fact, the same environment as your nearby forearm.

And microbes are everywhere within the digestive tract. A 2006 study by Elizabeth M. Bik of Stanford University and her colleagues demonstrates, for example, that the microbiota of the human stomach are both far more diverse and far more distinctive than previously imagined. The aggressive environment of the human stomach was considered until recently an inhospitable environment. All but the heartiest extremophiles would surely die in this acid vat of protein-degrading enzymes. But an analysis of telltale molecular signatures reveals 128 different species of stomach microorganisms. Fully half of these bacteria had never been cultured and had thus gone unnoticed. And these 128 resident species are not simply the descendants of an original colonist: They span eight phyla and reflect a broad cross-section of bacterial diversity. (One stomach even included Deinococcus, a genus previously found only in the effluent of nuclear-power plants and in arsenic-laden waste.) Not just the stomach, but the entire human gut turns out to be a patchwork of complex, dynamic, microbial ecosystems engaged in intimate conversations with their host. This new appreciation is based on the work of David A. Relman of Stanford University, Jeffery I. Gordon of Washington University, Claire M. Fraser-Liggett of the University of Maryland and others.

Many studies have underscored the distinct character of our microbial communities. The skin on our right forearm, for example, harbors a different microbial community than that of our left forearm. Both of these communities change over time. Even single regions of the body, such as the vagina, consist of multiple defined subenvironments, each with its own subset of tenants. The presence of such distinct communities is even more surprising when one thinks of the human body, as topologists do, as a cylinder with a hollow core. Given this kind of a picture, why exactly do distinct microbial communities persist on the inside and the outside of our bodies?

Part of the answer, as I suggested earlier, lies in the specialized environments that characterize the different sections of this hollow cylinder. As microbes colonize these specialized habitats, they further enhance the differences between environments. Bacterial guilds, in which one species's waste is another's food, begin to emerge. As these guilds expand, each new member contributes to the location-specific identity of the overall assemblage. Furthermore, these environments are all interconnected, and members of each community can and do travel far from home. We are now finding that certain groups of bacteria succeed in many different locations, whereas others seem tethered to single environments. We know there is movement, but the details of the microbial traffic patterns within our bodies are mostly unknown.